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Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes

Lindvall, Therese LU ; Karlsson, Jenny C LU ; Holmdahl, Rikard LU and Andersson, Åsa LU (2009) In Arthritis Research and Therapy 11(1).
Abstract
Introduction In a cross between two mouse strains, the susceptible B10.RIII (H-2r) and resistant RIIIS/J (H-2r) strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease in different experimental arthritis models, were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to EAE, control development of collagen-induced arthritis (CIA). Methods CIA, induced by immunisation with bovine type II collagen, was studied in Eae39 congenic and sub-interval congenic mice. Antibody titres were investigated with ELISA. Gene-typing was performed by microsatellite... (More)
Introduction In a cross between two mouse strains, the susceptible B10.RIII (H-2r) and resistant RIIIS/J (H-2r) strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease in different experimental arthritis models, were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to EAE, control development of collagen-induced arthritis (CIA). Methods CIA, induced by immunisation with bovine type II collagen, was studied in Eae39 congenic and sub-interval congenic mice. Antibody titres were investigated with ELISA. Gene-typing was performed by microsatellite mapping and statistics was calculated by standard methods. Results Experiments of CIA in Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10. RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titres. Two of the loci promoted disease and the third locus was protected against CIA development. By further breeding of mice with small congenic fragments, we identified a 3.2 mega base pair (Mbp) interval that regulates disease. Conclusions Disease-promoting and disease-protecting genes within the Eae39 locus on mouse chromosome 5 control susceptibility to CIA. A disease-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Arthritis Research and Therapy
volume
11
issue
1
publisher
BioMed Central
external identifiers
  • wos:000264563000033
  • scopus:60849096647
ISSN
1478-6362
DOI
10.1186/ar2597
language
English
LU publication?
yes
id
0807289c-0072-49d9-aea2-751b779c6cf1 (old id 1401650)
date added to LUP
2009-06-15 10:57:59
date last changed
2017-01-01 04:22:27
@article{0807289c-0072-49d9-aea2-751b779c6cf1,
  abstract     = {Introduction In a cross between two mouse strains, the susceptible B10.RIII (H-2r) and resistant RIIIS/J (H-2r) strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease in different experimental arthritis models, were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to EAE, control development of collagen-induced arthritis (CIA). Methods CIA, induced by immunisation with bovine type II collagen, was studied in Eae39 congenic and sub-interval congenic mice. Antibody titres were investigated with ELISA. Gene-typing was performed by microsatellite mapping and statistics was calculated by standard methods. Results Experiments of CIA in Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10. RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titres. Two of the loci promoted disease and the third locus was protected against CIA development. By further breeding of mice with small congenic fragments, we identified a 3.2 mega base pair (Mbp) interval that regulates disease. Conclusions Disease-promoting and disease-protecting genes within the Eae39 locus on mouse chromosome 5 control susceptibility to CIA. A disease-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases.},
  author       = {Lindvall, Therese and Karlsson, Jenny C and Holmdahl, Rikard and Andersson, Åsa},
  issn         = {1478-6362},
  language     = {eng},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes},
  url          = {http://dx.doi.org/10.1186/ar2597},
  volume       = {11},
  year         = {2009},
}